Hearing impairment has a profound effect on the American population, with almost thirty million people exhibiting some level of deafness or hearing loss. This disability impairs more people in terms of both numbers and economic impact than epilepsy, multiple sclerosis, spinal injury, stroke, and Huntington's and Parkinson's diseases combined. The goal of this proposal is to investigate the therapeutic potential of stem cells transplanted in the auditory system. To this end, the first aim is to study the cellular signaling between stem cells and cochlear explants in vitro. The upregulation of growth factors and cell migration will be measured from stem cells in co-culture with organ of Corti explants. The second aim is to exploit the developmental potential of stem cells by defining the in vitro conditions in which neural stem cells may transdifferentiate into cochlear cell types. To address this aim, we will attempt to prolong organ of Corti explant viability to optimize conditions for neural stem cell transdifferentiation. The final aim is to utilize the regenerative capacities of stem cells by transplanting them into deafened animal models. To accomplish this, neural stem cells will be transplanted into the internal auditory meatus of a denervated animal model. Lastly, stem cells will be transplanted into the otic capsule of a deafened animal model. The hypothesis is that the transplanted stem cells will respond to environmental cues and differentiate into cochlear cells. The hope is that transplanted stem cells will prove to be therapeutically beneficial to hearing loss. [unreadable] [unreadable]